It is proposed to continue biochemical studies of parasitic helminths that have been conducted over the previous 25 years of funding of AI 09483. Emphasis will continue to be placed on the intestinal nematode, Ascaris suum, the filariids, Brugia pahangi and Dipetalonema viteae, the cestode, Hymenolepis diminuta, and the trematode, Fasciola hepatica. Significant differences have been found at the level of overall metabolic pathways, including energy-yielding reactions, and at the more subtle levels of enzyme kinetics, regulation, structure and intercellular distribution. Such differences provide vulnerable sites for chemotherapeutic attack. Detailed metabolic studies of the parasitic helminths will continue in an effort to attain a more precise appreciation of the comparative aspects of host and parasite biochemistry which, is essential for a more basic understanding of host-parasite and parasite-drug interactions. The specific areas of investigation will include: a) The mechanism and tightly coupled regulation of succinate and volatile fatty acid formation in adult Ascaris, b) Comparative studies of energy-generating reactions in the mitochondria of Ascaris and other helminths. These reactions differ significantly from the corresponding reactions of mammalian systems and include substrate level phosphorylation, from the decarboxylation of succinate to propionate, as well as anaerobic, electron transport- associated ATP, c) The metabolism of the Ascaris reproductive system, which differs considerably from that of muscle, will be examined, d) New studies will be inaugurated to examine whether an Ascaris-like fumarate reductase system plays a role in mammalian "hibernating myocardium," e) Relationships between membrane lecithins, glycerophosphorlcholine and signal transduction will be investigated further, f) Techniques of electrophysiology and neuropharmacology will continue to be employed in studies of D. viteae by using microelectrodes placed in individual somatic cells, and g) The non-invasive technique of 32P and 13C nuclear magnetic resonance will continue to be employed to examine metabolism and drug action in intact Ascaris and F. hepatica.